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Series GSE74315 Query DataSets for GSE74315
Status Public on Jan 08, 2016
Title Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Newborn neurons enter an extended maturation stage, during which they acquire excitability characteristics crucial for development of presynaptic and postsynaptic connectivity. In contrast to earlier specification programs, little is known aboutthe regulatory mechanisms that control neuronal maturation. The Pet-1 ETS (E26 transformation-specific) factor is continuously expressed in serotonin (5-HT) neurons and initially acts in postmitotic precursors to control acquisition of 5-HT transmitter identity. Using a combination of RNA sequencing, electrophysiology, and conditional targeting approaches, we determined gene expression patterns in maturing flow-sorted 5-HT neurons and the temporal requirements for Pet-1 in shaping these patterns for functional maturation of mouse 5-HT neurons. We report a profound disruption of postmitotic expression trajectories in Pet-1 / neurons, which prevented postnatal maturation of 5-HT neuron passive and active intrinsic membrane properties, G-protein signaling, and synaptic responses to glutamatergic, lysophosphatidic, and adrenergic agonists. Unexpectedly, conditional targeting revealed a postnatal stage-specific switch in Pet-1 targets from 5-HT synthesis genes to transmitter receptor genes required for afferent modulation of 5-HT neuron excitability. 5-HT1a autoreceptor expression depended transiently on Pet-1, thus revealing an early postnatal sensitive period for control of 5-HT excitability genes. Chromatin immunoprecipitation followed by sequencing revealed that Pet-1 regulates 5-HT neuron maturation through direct gene activation and repression. Moreover, Pet-1 directly regulates the 5-HT neuron maturation factor Engrailed 1, which suggests Pet-1 orchestrates maturationthrough secondary postmitotic regulatoryfactors. The early postnatal switch in Pet-1targets uncovers a distinct neonatal stage-specific function for Pet-1, during which it promotes maturation of 5-HT neuron excitability.
Overall design 5-HT neuron mRNA profiles of E11.5, E15.5, and postnatal (P1-P3) wild type (WT) and Pet-1-/- mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500. Myc-tagged Pet-1 ChIP-seq was performed on E12.5 to E14.5 hindbrains and sequencing using NextSeq 500.
Contributor(s) Wyler SC, Spencer WC, Green NH, Rood BD, Crawford L, Craige C, Gresch P, McMahon DG, Beck SG, Deneris ES
Citation(s) 26843655
Submission date Oct 23, 2015
Last update date May 15, 2019
Contact name Evan Deneris
Organization name Case Western Reserve University
Department Neurosciences
Street address 2109 Adelbert Rd.
City Cleveland
State/province OH
ZIP/Postal code 44106
Country USA
Platforms (2)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (20)
GSM1917004 E11.5_WT1
GSM1917005 E11.5_WT2
GSM1917006 E11.5_WT3
BioProject PRJNA299652
SRA SRP065187

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Supplementary file Size Download File type/resource
GSE74315_Gene_expression_trajectories_E11.5_E15.5_PN.cuffdiff.txt.gz 1.5 Mb (ftp)(http) TXT
GSE74315_Gene_expression_trajectories_E11.5_E15.5_PN.matrix.txt.gz 783.4 Kb (ftp)(http) TXT
GSE74315_WT_vs_Pet1KO_5-HT_neuron_E15.5C_Clontech_cuffdiff.txt.gz 784.0 Kb (ftp)(http) TXT
GSE74315_WT_vs_Pet1KO_5-HT_neuron_E15.5N_NuGen_cuffdiff.txt.gz 781.1 Kb (ftp)(http) TXT
GSE74315_mycPet-1_ChIP_peaks.mm10.bed.gz 72.8 Kb (ftp)(http) BED
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